Cell-free and erythrocytic S-nitrosohemoglobin inhibits human platelet aggregation.
BACKGROUND
Nitric oxide (NO) and related molecules are thought to inhibit human platelet aggregation by raising levels of cGMP.


RESULTS
Both oxidative stress (reactive oxygen species) and hemoglobin (Hb) seem to oppose NO effects. A major fraction of NO in the blood is bound to thiols of Hb, forming S-nitrosohemoglobin (SNO-Hb), which releases the NO group on deoxygenation in the microcirculation. Here we show that (1) both cell-free and intraerythrocytic SNO-Hb (SNO-RBC) inhibit platelet aggregation, (2) the oxidation state of the hemes in Hb influences the response--SNO-metHb (which is functionally similar to SNO-deoxyHb) has greater platelet inhibitory effects than SNO-oxyHb, and (3) the mechanism of platelet inhibition by SNO-Hb is cGMP independent.


CONCLUSIONS
We suggest that the RBC has evolved a means to counteract platelet activation in small vessels and the proaggregatory effects of oxidative stress by forming SNO-Hb.
Pawloski
J R
JR
Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
Swaminathan
R V
RV
Stamler
J S
JS
D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002474:Cell-Free System; D006152:Cyclic GMP / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000737:chemistry / Q000502:physiology; D006454:Hemoglobins / Q000494:pharmacology*; D006801:Humans; D008706:Methemoglobin / Q000008:administration & dosage / Q000494:pharmacology; D010108:Oxyhemoglobins / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects* / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*
D006454:Hemoglobins; D010108:Oxyhemoglobins; D010975:Platelet Aggregation Inhibitors; C103574:S-nitrosohemoglobin; D008706:Methemoglobin; D006152:Cyclic GMP